Pertussis is a respiratory disease caused by bacteria that grow only on the ciliated epithelium of the respiratory tract. We are currently studying the cells involved in vaccine-mediated immunity in the respiratory tract in a mouse model of respiratory infection. We have found that the form of vaccine antigen as well as the site of immunization markedly change the kind of immune response observed. Acellular vaccine antigens, in soluble or particulate form, stimulate an antibody response and reduce infection when given by either a respiratory or a parenteral route. A whole cell vaccine, composed of formalinized B. pertussis, stimulates an antibody response when given by a parenteral route, but not by a respiratory route, and yet is highly protective against infection when given by the respiratory route. This protection is antigen specific, is not due to a lipid-A stimulated inflammatory response, and may be mediated by vir-independent gene products of B. pertussis. This protection requires mature T cells, as immunized nude mice are not protected. Populations of T cells that proliferate specifically in response to antigen and secrete cytokines are generated in the draining lymph nodes of the lungs of mice immunized intranasally with either form of pertussis vaccine. We are have established T cell lines from mice vaccinated with formalin fixed whole B. pertussis; these T cells secrete gamma-interferon, but neither IL-4 nor IL-10 and thus have the character of a TH-1 response. Conversely, T cell lines from mice vaccinated with an acellular vaccine antigen, filamentous hemagglutinin, secrete IL-4 and IL-10, but not gamma-interferon, and thus have the character of a TH-2 response. Cell depletion experiments as well as passive protection experiments and analysis of cytokine mRNA are now in progress in order to study in a detailed fashion, the role of specific T cell populations in protective respiratory immunity to B. pertussis infection.